We propose the establishment of an International Center for Research on Complementary and Alternative Medicine (ICRC) led by investigators from the Harvard Medical School (US), The Chinese University of Hong Kong (CUHK; China) and Keio University (Japan) to systematically evaluate traditionally used East Asian (Chinese and Japanese) botanicals for their anti-cancer properties. In Phase I of this ICRC grant, co-investigators developed the core capacity to identify, procure, authenticate, extract, fractionate and test candidate botanicals both singly and in combination for activity relating to cancer biology. 45 botanicals traditionally used to treat cancer were selected, purchased, extracted and separated into fractions. A total of 1025 fractions were systematically tested and many were found to exhibit anti-cancer properties based on a range of bioassays. However, when voucher samples of Phase I botanicals were authenticated, some were found to have been adulterated or misidentified. In Phase II, our objectives are: (1) to establish and maintain a library of authenticated East Asian botanical extracts for scientific evaluation, beginning with 20 botanicals selected based on Phase I data (Botanical Core); (2) to create a high-throughput and combinatorial Screening Core to test botanicals individually and in combination for their activity in bioassays relating to cancer (Projects 1 and 2) and effects on immune regulators (Project 3); (3) to test extracts and fractions with optimal activity in relevant animal tumor models (Projects 1, 2 and 3); and (4) to enhance research capacity at CUHK and Keio University. Importantly, a Botanical Core will be established to obtain candidate botanicals directly from known farms in China prior to authentication and systematic evaluation. The Screening Core will coordinate bioassay results and the Administrative Core will coordinate all administrative activities. This ICRC brings together an unprecedented team of investigators with expertise in traditional Chinese and Japanese medicine, authentication and acquisition of Asian botanicals, cancer research and clinical oncology to systematically apply state-of-the-art technologies to evaluate East Asian botanicals for their anticancer properties. We are confident that this approach will enable our non-US partner institutions to independently apply for subsequent NIH awards. The exchange of faculty and fellows within this ICRC will create a cadre of investigators equipped to continue their collaborative research in all three participating countries. These investigators will help shape the evolution of integrative and global medicine research in the coming decades. The results of this international partnership will contribute to our understanding of East Asian botanicals as potential cancer therapies and will, we believe, contribute to sustaining and further developing East Asian medical traditions.